The purpose of the work proposed is to examine the interrelationships between cardiac trans membrane sodium fluxes and myocardial calcium movements. The use of cation-selective antibiotic ionophores will permit controlled alterations of intracellular cation concentrations without necessitating modification of the composition of the extracellular medium or of tissue activity. Perturbation of the normal monovalent cation gradients will be quantitated by use of 24Na and 42K in the rabbit interventricular septal preparation. Changes in the cellular distribution of H plus cations will be measured by the DMO method for determination of intracelluar pH. Subsequent alterations in Ca cations metabolism will be monitored using 45Ca movements in the septal preparation and by measurements of the contractile state of septal and papillary muscle preparations. Initial experiments will be directed toward quantitation of the ionophore-induced ion fluxes. Subsequent work will couple administration of the ionophore with physiological and pharmacological inotropic interventions such as, altered rates of stimulation and cardiac glycosides in order to investigate the locations and characteristics of sodium-sensitive Ca ions movements. Information acquired from these investigations will be applied to investigations of drug induced alterations of cardiac ion exchanges and to the study of several experimental models of heart disease including myocardia made ischemic, hypoxic and acidotic.